Clinical Trials Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 21, 2018; 24(23): 2508-2517
Published online Jun 21, 2018. doi: 10.3748/wjg.v24.i23.2508
Clinical and prognostic significance of Raf kinase inhibitory protein expression in gastrointestinal stromal tumors
Yang Wang, Juan-Juan Chen, Xiao-Fei Wang, Qiang Wang
Yang Wang, Juan-Juan Chen, Xiao-Fei Wang, Qiang Wang, Department of Gastrointestinal Surgery, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
Author contributions: Wang Y designed research; Wang Y performed research; Wang Y and Chen JJ contributed new reagents or analytic tools; Wang Y and Wang XF analyzed data; Wang Y wrote the paper; Wang Q edited the paper and provided primary revised opinion.
Institutional review board statement: The study was reviewed and approved by Sheng-Jing Hospital of China Medical University Institutional Review Board.
Informed consent statement: The patient involved in this study gave her written informed consent authorizing use and disclosure of her protected health information.
Conflict-of-interest statement: All the authors have no conflicts of interests to declare.
CONSORT 2010 statement: the guidelines of the CONSORT 2010 Statement have been adopted.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Qiang Wang, PhD, Doctor, Professor, Department of Gastrointestinal Surgery, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China.
Telephone: +86-24-96615
Received: March 14, 2018
Peer-review started: March 14, 2018
First decision: March 30, 2018
Revised: April 5, 2018
Accepted: April 26, 2018
Article in press: April 26, 2018
Published online: June 21, 2018

To detect the expression of Raf kinase inhibitory protein (RKIP) in gastrointestinal stromal tumors (GISTs) and to analyze its relationship with clinicopatholgical characteristics and prognosis of this disease.


Sixty-three patients with pathologically diagnosed GISTs who underwent surgical resection at the Shengjing Hospital of China Medical University from January 2011 to January 2015 and had complete clinical, pathological, and follow-up data were included. Immunohistochemical method was used to detect the expression of RKIP in GIST tissue samples from these patients. Kaplan-Meier method was used to calculate the survival rate of 60 patients with complete follow-up data, and Cox regression analysis was performed to identify factors affecting the prognosis of patients GISTs to evaluate further the diagnostic and prognostic value of RKIP in GISTs.


In GIST tissues, RKIP positive signals, manifesting as brownish yellow or brown granules, were located in the cytoplasm or on the membrane. Of 63 tissue samples included in this study, 34 (54%) were positive and 29 (46%) were negative for RKIP expression. Statistical analysis showed that RKIP expression in GISTs was significantly associated with tumor size, National Institutes of Health (NIH) risk grade, and mucosal invasion, but had no significant association with age, gender, tumor location, or the number of mitotic figures. Univariate Kaplan-Meier analysis revealed that the 1-, 3-, and 5-year survival rates were 94.4%, 89.2%, and 80.5% for patients with positive RKIP expression, and 88.6%, 68.2%, and 48.2% for patients with negative RKIP expression, suggesting that patients with high RKIP expression had significantly higher survival rates than those with low expression (Log-rank test, P = 0.0015). Cox regression analysis demonstrated that NIH risk grade was significantly associated with the prognosis of GISTs (P = 0.037), suggesting that NIH risk grade is a significant predictor of the prognosis of GISTs. RKIP expression had a tendency to predict the survival of GISTs (P = 0.122), suggesting that RKIP expression may have appreciated value to predict the prognosis of GISTs.


This study demonstrated that: (1) RKIP expression in GISTs is associated with tumor size, NIH risk grade, and mucosal invasion, and low or no expression of RKIP predicts a high malignancy potential; (2) high RKIP correlates positively with the survival of patients with GISTs; and (3) RKIP expression has appreciated value for predicting the survival of patients with GISTs, although it is not an independent prognostic factor in GISTs.

Keywords: Gastrointestinal stromal tumors, Raf kinase inhibitory protein, Immunohistochemistry, Survival analysis

Core tip: In this study, the expression of Raf kinase inhibitory protein (RKIP) in gastrointestinal stromal tumors (GISTs) was examined by immunohistochemistry. We explored the relationship between RKIP protein expression and survival and prognosis in a large sample of GIST patients in China. RKIP protein expression was correlated with tumor growth, differentiation, malignancy, and the prognosis of the tumor. Our findings provide evidence for the diagnosis and prognosis assessment of GIST and offer new tumor treatment targets in GIST.